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首页> 外文期刊>Life sciences >Adenosine receptor antagonists and behavioral activation in NF-kappaB p50 subunit knockout mice.
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Adenosine receptor antagonists and behavioral activation in NF-kappaB p50 subunit knockout mice.

机译：NF-κBp50亚基敲除小鼠中的腺苷受体拮抗剂和行为激活。

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AIMS: Our previous work revealed that mice lacking the p50 subunit of transcription factor nuclear factor kappa B (NF-kappaB) (p50 KO mice) and genetically intact F2 mice have similar locomotion under basal conditions, yet p50 KO mice show greater locomotor activation after caffeine ingestion. In this report, we test whether KO mice display altered caffeine pharmacokinetics or increased caffeine-induced DA turnover relative to F2 mice, and evaluate the impact of intraperitoneal administration of specific adenosine and DA receptor antagonists on locomotor activity. MAIN METHODS: Concentrations of DA and caffeine were measured using high performance liquid chromatography. DA turnover was measured after treatment of mice with an inhibitor of tyrosine hydroxylase. Locomotor activity was measured using telemetry. KEY FINDINGS: The data reveal that 1) caffeine concentrations in blood and brain are similar in KO and F2 mice after oral or intraperitoneal administration; 2) KO mice show greater DA turnover under basal conditions, but turnover is similar in both strains after caffeine administration; 3) the specific A2AAR antagonist SCH 58261 induces greater locomotion in KO versus F2 mice; and 4) the activating effect of SCH 58261 in KO mice is prevented by prior treatment with the D2R antagonist raclopride. SIGNIFICANCE: These findings support the conclusions that 1) A2AAR has a major impact on behavioral activation of p50 KO mice, and 2) D2R mediated neurotransmission is important to this effect.
机译：目的：我们先前的工作表明，缺乏转录因子核因子κB（NF-kappaB）p50亚基的小鼠（p50 KO小鼠）和遗传上完整的F2小鼠在基础条件下具有相似的运动，而p50 KO小鼠在运动后具有更大的运动活化咖啡因摄入。在此报告中，我们测试了KO小鼠相对于F2小鼠是否表现出改变的咖啡因药代动力学或增加的咖啡因诱导的DA周转率，并评估了腹膜内给予特定腺苷和DA受体拮抗剂对运动能力的影响。主要方法：使用高效液相色谱法测定DA和咖啡因的浓度。在用酪氨酸羟化酶抑制剂治疗小鼠后，测量DA周转率。使用遥测法测量运动活动。主要发现：数据显示：1）口服或腹膜内给药后，KO和F2小鼠血液和脑中咖啡因浓度相似; 2）在基础条件下，KO小鼠显示出更高的DA转化率，但是咖啡因给药后两种菌株的转化率相似; 3）与F2小鼠相比，特异性A2AAR拮抗剂SCH 58261在KO中诱导更大的运动。 4）通过事先用D2R拮抗剂雷氯必利治疗来预防SCH 58261在KO小鼠中的激活作用。意义：这些发现支持以下结论：1）A2AAR对p50 KO小鼠的行为激活有重要影响，并且2）D2R介导的神经传递对此效应很重要。

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